Type 2 diabetes mellitus (DM-2) is a common global disease characterized by insulin deficiency and insulin insensitivity. DM-2 is considered to be a serious disease creating a health problem associated with a high morbidity and mortality, and is the sixth leading cause of death in the United States [Miniño et al, 2007, National Vital Statistical Report, 55]. It is expected that the number of diabetic patients could increase to 300 million worldwide by the year of 2025 [King et al, 1998, Diabetes Care, 21, 1414-31]. In the United States, 7 percent of the population—20.8 million children and adults—are affected by diabetes [French, 2007, Inside, 12, 46-7] and it costs the United States an estimated $132 billion in 2002 in medical expenditures and lost productivity [Hogan et al, 2003, Diabetes Care, 26, 917-32]. The treatment methods for DM-2 include use of insulin, insulin analogs or modified insulin, enhancing insulin release and insulin action, inhibiting hepatic glucose production, and inhibiting glucose uptake [Moller, 2001, Nature, 414, 821-27]. In addition to these therapeutic agents, traditional medicines for the treatment of DM-2 are also used throughout the world. More than 1,200 species of organisms have been used ethnopharmacologically or experimentally to treat symptoms of DM-2 [Marles and Farnsworth, 1996, Protocol J. Botanical Med., 1, 85-137].
It is generally recognized that the rapidly rising prevalence of obesity represents a serious public heath problem in the United States. According to data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES), nearly two-thirds (64.5%) of the adult population of the Unites States are overweight compared to 55.9% as detailed by the NHANES III research conducted between 1988 and 1994. The prevalence of obesity has also increased dramatically from 22.9% to 30.5% over the same period. The increasing number of obese people is likely at a high risk of developing a variety of obesity-related diseases include diabetes [Flegal et al, 2002, JAMA. 288, 1723-1727 and Kuczmarski et al 1994, JAMA. 272, 205-221].
Fraxinus excelsior L., a plant of the Oleaceae family, is commonly known as “Common Ash” or “European Ash” in the countries of temperate Asia and Europe [Gilman and Watson, 1993, Fact Sheet ST-264, November]. This plant is also widely distributed throughout Tafilalet, the southeastern region of Morocco, and is known there as “l'ssane l'ousfour.” The Tafilalet region has been considered among the regions of Morocco where phytotherapy knowledge is the most developed [Eddouks et al, 2002, J. Ethnopharmacol. 82, 97-103]. Recent studies have indicated that F. excelsior (FE) possesses antibacterial and antioxidant activities. Methanol extract of FE showed potent antioxidant activity with RC50 of 1.35×10−2 in the qualitative α,α-diphenyl-β-picrylhydrazyl (DPPH) assay. The n-hexane and dichloromethane extract of FE were also active against eight species of Gram-positive and Gram-negative pathogenic bacteria tested including methicillin-resistant Staphylococcus aureus with minimal inhibitory concentration (MIC) values within 1.25×10−1 mg/mL [Middleton et al, 2005, Indian J. Pharma. Res., 2, 81-6]. The hypotensive effect of FE on both normotensive and spontaneously hypertensive rats was reported. Daily oral administration of the aqueous extract of FE seeds produced a significant decrease in systolic blood pressure and significantly enhanced the urination in both types of rats [Eddouks et al, 2005, J. Ethnopharmacol., 99, 49-54]. The aqueous extracts of FE seed displayed potent hypoglycemic and anti-hyperglycemic activity in normal and streptozotocin-induced (STZ) rats without affecting basal plasma insulin concentrations [Maghrani et al, 2004, J. Ethnopharmacol., 91, 309-16]. The Phlorizin-like effect of inhibition of renal glucose reabsorption might be one of the mechanisms for the hypoglycemic effect of FE [Eddouks et al, 2004, J. Ethnopharmacol., 94, 149-54].
FE was reported to mainly contain coumarins, secoiridoids, and phenylethanoids. [Kostova and lossifova, 2007, Fitoterapia 78, 85-106]. The secoiridoids found in FE are derived from oleoside. These types of secoiridoids exists only in plants of the family Oleaceae [Egan et al, 2004, Biochem. Sys. Ecol., 32, 1069-71].